Ferumoxytol versus placebo in iron deficiency anemia: efficacy, safety, and quality of life in patients with gastrointestinal disorders

Figures & data

Figure 1 Patient disposition for the subgroup of patients with IDA and GI disorders.

Abbreviations: IDA, iron deficiency anemia; GI, gastrointestinal; AE, adverse event.

Table 1 Baseline characteristics of the subgroup of patients with IDA and GI disorders (intent-to-treat population)

Baseline characteristics	GI disorders subgroup			Overall IDA group
	Ferumoxytol (n=173)	Placebo (n=58)	Total (n=231)	Total (N=808)
Demographics
Age (years), mean (SD)	47.4 (16.85)	52.1 (15.93)	48.6 (16.72)	45.1 (13.76)
Sex, n (%)
Female	136 (78.6)	44 (75.9)	180 (77.9)	720 (89.1)
Male	37 (21.4)	14 (24.1)	51 (22.1)	88 (10.9)
Race, n (%)
Asian	33 (19.1)	6 (10.3)	39 (16.9)	130 (16.1)
Black/African-American	16 (9.2)	5 (8.6)	21 (9.1)	202 (25.0)
White	120 (69.4)	45 (77.6)	165 (71.4)	451 (55.8)
Other/multiracial	4 (2.3)	2 (3.4)	6 (2.6)	25 (3.1)
Ethnicity, n (%)
Hispanic/Latino	19 (11.0)	5 (8.6)	24 (10.4)	144 (17.8)
Non-Hispanic/latino	154 (89.0)	53 (91.4)	207 (89.6)	664 (82.2)
Clinical, mean (SD)
Baseline Hgb level (g/l)	89 (8.9)	87 (7.3)	88 (8.5)	89 (8.9)
Baseline TSAT (%)	6.5 (12.97)	4.7 (3.53)	6.0 (11.67)	6.6 (11.51)
Baseline FACIT-Fatigue	22.4 (11.7)	22.1 (11.4)
Baseline lASA, mean, (SD)
Quality of life	46.1 (21.9)	43.4 (23.4)
Activities of daily living	43.2 (22.3)	38.7 (22.9)
Energy level	33.7 (20.3)	33.2 (22.2)

Note: Baseline values were obtained on Day 1 prior to injection of study drug.

Abbreviations: FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy–Fatigue; GI, gastrointestinal; Hgb, hemoglobin; IDA, iron deficiency anemia; lASA, linear Analog Scale Assessment; SD, standard deviation; TSAT, transferrin saturation.

Figure 2 Mean Hgb values (g/l) from baseline to Week 5 in patients with IDA and GI disorders (intent-to-treat population).

Notes: ^#The first ferumoxytol dose was administered at baseline. *P<0.0001 for mean change from baseline.
Abbreviations: Hgb, hemoglobin; IDA, iron deficiency anemia; GI, gastrointestinal.

Table 2 Efficacy end points in the subgroup of patients with IDA and GI disorders (intent-to-treat population)

Efficacy end point	Treatment groups		P-value
	Ferumoxytol (n=173)	Placebo (n=58)
Primary end point
Proportion of patients with ≥20 g/l Hgb increase at any time from baseline to Week 5, n (%)	142 (82.1)	1 (1.7)	<0.001
Alternative primary end pointa
ΔHgb (g/l), mean	28.0	−1.0	<0.001
Secondary end points
Proportion of patients with Hgb ≥120 g/l at any time from baseline to Week 5, n (%)	89 (51.4)	0	<0.001
ΔTSAT (%), mean (SD)	11.5 (15.01)	0.2 (2.27)	<0.001
Patient-reported outcomes,a mean (SD)
ΔFACIT-Fatigue score	11.1 (11.5)	7.4 (8.7)	0.031
ΔSF-36-Physical functioning score	4.6 (9.5)	0.8 (7.8)	0.005
ΔSF-36-Role-Physical score	5.6 (10.2)	2.6 (9.6)	0.045
ΔSF-36-Bodily pain score	2.9 (9.3)	2.0 (11.0)	0.557
ΔSF-36-General health score	3.4 (8.4)	0.7 (6.1)	0.023
ΔSF-36-Vitality	9.7 (11.9)	3.9 (8.3)	<0.001
ΔSF-36-Social functioning score	7.0 (12.5)	1.1 (9.5)	0.001
ΔSF-36-Role-Emotional score	4.7 (12.8)	1.5 (12.9)	0.103
ΔSF-36-Mental health score	5.8 (11.6)	0.6 (8.3)	<0.002
ΔSF-36-Physical component summary score	3.7 (7.6)	1.7 (6.8)	0.071
ΔSF-36-Mental component summary score	7.0 (12.1)	1.5 (9.5)	0.002
ΔSF-36-6D score	0.10 (0.14)	0.03 (0.11)	<0.001
ΔlASA-Energy level score	16.7 (26.2)	9.8 (19.0)	0.086
ΔlASA-Activities of daily living score	13.4 (27.2)	9.8 (21.8)	0.385
ΔlASA-Quality of life score	11.8 (27.7)	8.2 (18.0)	0.386

Note:

a Change from baseline to Week 5 unless otherwise stated.

Abbreviations: FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy–Fatigue; GI, gastrointestinal; Hgb, hemoglobin; IDA, iron deficiency anemia; lASA, linear Analog Scale Assessment; SD, standard deviation; SF-36, 36-Item Short-Form Health Survey; TSAT, transferrin saturation.

Figure 3 Mean TSAT values from baseline to Week 5 in patients with IDA and GI disorders (intent-to-treat population).

Notes: ^#The first ferumoxytol dose was administered at baseline. *P<0.0001 for mean change from baseline.
Abbreviations: IDA, iron deficiency anemia; GI, gastrointestinal; TSAT, transferrin saturation.

Figure 4 SF-36 domain scores at baseline in patients with IDA and GI disorders (intent-to-treat population).

Abbreviations: IDA, iron deficiency anemia; GI, gastrointestinal; SF-36, 36-item Short-Form Health Survey; SD, standard deviation.

Figure 5 Patient-reported outcomes at baseline and Week 5 in patients with IDA and GI disorders (intent-to-treat population).

Notes: The figure shows mean change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)–Fatigue scores. *P<0.05 vs placebo. The first ferumoxytol dose was administered at baseline. FACIT-fatigue score is 0-52, based on 13 questions scored 0–4.
Abbreviations: IDA, iron deficiency anemia; GI, gastrointestinal.

Figure 6 Patient-reported outcomes at baseline and Week 5 in patients with IDA and GI disorders (intent-to-treat population).

Notes: The figure shows mean change from baseline in the 36-Item Short-Form Health Survey (SF-36) domain scores. *P<0.05 vs placebo. The first ferumoxytol dose was administered at baseline. Error bars indicate 95% confidence intervals.
Abbreviations: IDA, iron deficiency anemia; GI, gastrointestinal.

Figure 7 Patient-reported outcomes at baseline, Week 3, and Week 5 in patients with IDA and GI disorders (intent-to-treat population).

Notes: Mean change from baseline in linear Analog Scale Assessment (lASA) domain scores is shown. The first ferumoxytol dose was administered at baseline. Error bars indicate 95% confidence intervals.
Abbreviations: IDA, iron deficiency anemia; GI, gastrointestinal.

Table 3 Summary of TEAEs in patients with IDA and GI disorders (safety population)

AE category	Treatment group				Total (N=231)
	Ferumoxytol (n=173)		Placebo (n=58)
	Events, n	Patients, n (%)	Events, n	Patients, n (%)	Events, n	Patients, n (%)
All TEAEs	188	84 (48.6)	60	26 (44.8)	248	110 (47.6)
Treatment-related AEs	37	20 (11.6)	4	2 (3.4)	41	22 (9.5)
SAEs	6	5 (2.9)	2	2 (3.4)	8	7 (3.0)
Treatment-related SAEs	1	1 (0.6)	0	0	1	1 (0.4)
Protocol-defined AEs of special interesta	7	6 (3.5)	1	1 (1.7)	8	7 (3.0)
Composite cardiovascular AE end pointb	0	0	0	0	0	0
AEs resulting in temporary discontinuation of study drug	0	0	0	0	0	0
AEs resulting in permanent discontinuation of study drug	9	5 (2.9)	0	0	9	5 (2.2)
AEs resulting in study discontinuation	4	2 (1.2)	0	0	4	2 (0.9)
Death	0	0	0	0	0	0
TEAEs reported in ≥2% of patients
Headache	9	8 (4.6)	3	3 (5.2)	12	11 (4.8)
Nausea	10	9 (5.2)	2	2 (3.4)	12	11 (4.8)
Dizziness	7	6 (3.5)	2	2 (3.4)	9	8 (3.5)
Diarrhea	5	5 (2.9)	2	2 (3.4)	7	7 (3.0)
Urinary tract infection	5	5 (2.9)	1	1 (1.7)	6	6 (2.6)
Nasopharyngitis	5	5 (2.9)	2	2 (3.4)	7	7 (3.0)
Peripheral edema	5	5 (2.9)	1	1 (1.7)	6	6 (2.6)
Vomiting	5	5 (2.9)	0	0	5	5 (2.2)
Back pain	4	4 (2.3)	1	1 (1.7)	5	5 (2.2)
Fatigue	3	3 (1.7)	2	2 (3.4)	5	5 (2.2)
Pain in extremity	4	4 (2.3)	0	0	4	4 (1.7)
Abdominal pain	3	3 (1.7)	3	2 (3.4)	6	5 (2.2)
Dyspnea	5	5 (2.9)	1	1 (1.7)	6	6 (2.6)
Anemia	1	1 (0.6)	2	2 (3.4)	3	3 (1.3)

Notes:

a Includes moderate-to-severe hypotension requiring medical intervention or hospitalization, acute decreases in systolic blood pressure from baseline of ≥30% during the 60-minute postdose observation period, hypotension associated with symptoms, systemic allergic reactions (anaphylaxis/anaphylactoid reactions), and milder symptoms of hypersensitivity.

b Includes myocardial infarction, heart failure, moderate-to-severe hypertension, and hospitalization due to any cardiovascular cause.

Abbreviations: AE, adverse event; GI, gastrointestinal; IDA, iron deficiency anemia; SAE, serious adverse event; TEAE, treatment-emergent adverse event.